(a) Field of the Invention
The present invention relates to a method for preparing organic microbubble complex particles, organic microbubble complex particles, and a contrast agent, and more particularly, to organic microbubble complex particles that have high uniformity of particle size and excellent long term shape stability and storage stability, a preparation method thereof, and a contrast agent having an excellent enhancement effect, stability, and excellent reproducibility of ultrasound contrast.
(b) Description of the Related Art
A bubble is a spherical body consisting of a gas suspending in a liquid. A bubble of a stable structure may be applied in the fields of acoustic bandgap materials and functional light-weight materials, as well as in food and cosmetic industries.
Further, bubbles may be used for biomedical applications such as contrast-enhanced ultrasonography, drug or gene delivery by ultrasound, and the like, and bubbles of a micrometer size that have a high compression rate and scattering elasticity compared to an aqueous medium are also used as an ultrasound contrast agent.
Ultrasound contrast agents have been in development since Gramiak and Shah discovered that an ultrasound signal is enhanced after injecting microbubbles into a blood vessel in 1968, and currently, myocardial perfusion is evaluated by administering microbubbles that can enhance reflection of ultrasound and indirectly measuring ultrasound reflectivity of the myocardium.
That is, if a contrast agent is administered and then ultrasound is applied, the ultrasound is reflected by microbubbles in the contrast agent to more clearly show an image of the myocardium.
Commonly, in ultrasound contrast agents, bubbles formed by injecting a gas such as nitrogen and the like in an aqueous medium have been used, but according to the previous method, it was difficult to prepare bubbles having a uniform size and required properties, and the prepared bubbles had a limitation in that they could not maintain the shape or exist in an aqueous medium for a long time required for diagnosis.
Recently, a method of preparing bubbles by adding a surfactant or other surface stabilizing materials to an aqueous medium and injecting gas has been known. However, although the prepared bubbles may secure structural stability to a specific degree, they have limitations in that it is difficult to mass-produce them with a constant size, they may not have sufficient performance as ultrasound contrast agents such as a high enhancement effect or excellent reproducibility of ultrasound contrast, and it is not easy to keep them for a long time after preparation.